# Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials

Source: https://onco.cc/key-papers/paper-early-breast-cancer-trialists-collaborative-group-ebctcg-lancet/  
OnCo record `paper-early-breast-cancer-trialists-collaborative-group-ebctcg-lancet` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one technology page and one term page, indexed on Europe PMC as PubMed record 26211824 and published in The Lancet; the citing pages link this DOI, which is how the record was matched.

## Summary

Background: Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and benefits of adjuvant bisphosphonate treatment in breast cancer.

Methods: We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality. Primary subgroup investigations were site of first distant recurrence (bone or other), menopausal status (postmenopausal [combining natural and artificial] or not), and bisphosphonate class (aminobisphosphonate [eg, zoledronic acid, ibandronate, pamidronate] or other [ie, clodronate]). Intention-to-treat log-rank methods yielded bisphosphonate versus control first-event rate ratios (RRs).

Findings: We received data on 18,766 women (18,206 [97%] in trials of 2-5 years of bisphosphonate) with median follow-up 5·6 woman-years, 3453 first recurrences, and 2106 subsequent deaths. Overall, the reductions in recurrence (RR 0·94, 95% CI 0·87-1·01; 2p=0·08), distant recurrence (0·92, 0·85-0·99; 2p=0·03), and breast cancer mortality (0·91, 0·83-0·99; 2p=0·04) were of only borderline significance, but the reduction in bone recurrence was more definite (0·83, 0·73-0·94; 2p=0·004). Among premenopausal women, treatment had no apparent effect on any outcome, but among 11 767 postmenopausal women it produced highly significant reductions in recurrence (RR 0·86, 95% CI 0·78-0·94; 2p=0·002), distant recurrence (0·82, 0·74-0·92; 2p=0·0003), bone recurrence (0·72, 0·60-0·86; 2p=0·0002), and breast cancer mortality (0·82, 0·73-0·93; 2p=0·002). Even for bone recurrence, however, the heterogeneity of benefit was barely significant by menopausal status (2p=0·06 for trend with menopausal status) or age (2p=0·03), and it was non-significant by bisphosphonate class, treatment schedule, oestrogen receptor status, nodes, tumour grade, or concomitant chemotherapy. No differences were seen in non-breast cancer mortality. Bone fractures were reduced (RR 0·85, 95% CI 0·75-0·97; 2p=0·02).

Interpretation: Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival, but there is definite benefit only in women who were postmenopausal when treatment began.

Funding: Cancer Research UK, Medical Research Council.

Indexed on Europe PMC as PubMed record 26211824 (DOI 10.1016/s0140-6736(15)60908-4). Matched by DOI alone: one technology page and one term page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: The Lancet
- Year: 2015
- DOI: 10.1016/s0140-6736(15)60908-4
- Authors: Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
- What it means: One technology page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Lancet 2015: https://doi.org/10.1016/s0140-6736(15)60908-4
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26211824/
- Europe PMC: https://europepmc.org/article/MED/26211824

## Connected records

- technologies: [Bone-modifying agents (bisphosphonates, denosumab)](https://onco.cc/technologies/bone-modifying-agents/)
- terms: [Seed and soil hypothesis of metastasis (Paget)](https://onco.cc/terms/seed-and-soil-hypothesis/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)

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